Tag Archives: IBD

The diet-microbiome connection in inflammatory bowel disease

Much remains mysterious about the factors influencing human inflammatory bowel disease (IBD), but one aspect that has emerged as a key contributor is the gut microbiome, the collection of microorganisms dwelling in the intestines.

Diet is known to profoundly affect this microbial community, and special diets have been used as therapies for intestinal disorders including Crohn’s disease in people. They’re also commonly used in dogs, which can develop a chronic intestinal disease that mirrors many features of Crohn’s.

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Tracking dogs on a prescription diet for an intestinal disease, researchers found that those that responded well shared a suite of changes to their microbiome. (Image: Penn Vet)

In a new study published in the journal Microbiome, researchers from the University of Pennsylvania investigated the connection between a prescription diet, the gut microbiome, and a successful entry into disease remission in pet dogs receiving treatment at Penn Vet’s Ryan Veterinary Hospital. They discovered key features of the microbiome and associated metabolic products that appeared only in dogs that entered disease remission. A type of bacteria that produces these compounds, known as secondary bile acids, alleviated disease in a mouse model. And comparing the impact of diet on the dog’s microbiome with that seen during diet therapy in children with Crohn’s, the study team found notable similarities.

“The bacteria in the gut are known to be a really important factor in tipping the scales toward disease,” says Daniel Beiting, senior author on the work and an assistant professor in the School of Veterinary Medicine. “And the environmental factor that seems to contribute the most to rapid changes in the microbiome is what you eat. Given that dogs’ microbiomes are extremely similar to those of humans, we thought this was an intriguing model to ask, ‘Could diet be impacting this disease through an impact on the microbiome?’”

To begin pursuing this question required treating a population of pet dogs with canine chronic enteropathy (CE), a chronic condition involving weight loss and gut inflammation, diarrhea, occasional vomiting, loss of appetite, and a chronic relapsing and remitting, just as seen in Crohn’s disease. The study involved 53 dogs, 29 with CE being treated at Penn Vet’s Ryan Veterinary Hospital, and 24 healthy controls.

Researchers collected stool samples at the outset of the study and at different times as the sick dogs began a prescription diet to treat their disease. Using advanced genetic sequencing techniques, the team developed a catalog of the microbes present in the stool, a stand-in for the animals’ gut microbiome. They also collected information about the metabolic products present in the stool.

“That gives us a functional read-out of the microbiome,” says Beiting. “It doesn’t just tell us who is there but also what they’re doing.”

Twenty of the 29 sick dogs quickly entered remission. Together, the genomic and metabolite analyses revealed characteristic changes in these dogs. In particular, those that responded well to the diet tended to have an increase in metabolites known as secondary bile acids. These are produced when certain microbes in the gut consume the bile that is released by the liver.

One of these “good” microbes that can give rise to secondary bile acids was the bacterium Clostridium hiranonis, which the researchers found in greater numbers in dogs that went into remission. Dogs that responded well to the diet also had fewer harmful bacteria, such as Escherichia coli and Clostridium perfringens after starting treatment.

To learn more about what these apparent markers of remission were doing, the team took bacteria from the dogs—both when they were sick and after they had entered remission—and grew them in the lab.

“Having these organisms gave us the opportunity to test our hypothesis about what actually causes remission,” says Shuai Wang, a postdoc at Penn Vet and the study’s lead author.

Taking the secondary bile acids found to be associated with remission, the researchers applied them to the E. coli and C. perfringens grown from the sick dogs and found the bile acids inhibited their growth. They also gave C. hiranonis from the dogs to mice with a form of inflammatory bowel disorder to see if the bacteria could reduce disease in a different animal model.

“We observed a stabilization of secondary bile acid levels and reduced inflammation,” Wang says.

“This allowed us to show that secondary bile acids and C. hiranonis aren’t just biomarkers of remission,” says Beiting, “they can actually effect change. Bile acids can block the growth of pathogens, and C. hiranonis can improve gut health in mice.”

As a final step, the researchers looked to a dataset taken from children with Crohn’s disease who were treated with a specialized liquid diet known as exclusive enteral nutrition. Youngsters who responded to the therapy had an increase in numbers of the bacteria species Clostridium scindens, which, like C. hiranonis, is a potent producer of secondary bile acids.

The authors say the findings offer hope for better dietary therapies for IBD, perhaps ones that deliver “good” bacteria such as C. scindens or C. hiranonis while suppressing disease-associated species.

“Similar environmental exposures of dogs and children make the canine IBD model an excellent model of pediatric inflammatory bowel disease,” says Robert N. Baldassano, a study coauthor and pediatric gastroenterologist at Children’s Hospital of Philadelphia. “This study has greatly improved our knowledge of pediatric IBD and will lead to new therapies for children suffering with this disease.”

Source:  Penn Today

Your dog’s poo

They say that the eyes are the window to the soul; in many ways your dog’s poo is a window on their health.

(I never thought I’d see the day when I wrote about poop – but there’s a first time for everything.)

Have you noticed that the color of your dog’s poo changes with what they are fed?  For example, if you are feeding raw venison, chances are the poo is quite dark.

If, however, the stool has a noticeably black color such as in this photo, this can indicate digested blood and you should be off the vet for a check (don’t be shy, take a sample with you!).

A yellow or slightly green tone indicates a rapid transit time in the bowel, typical if your dog has had diarrhea, as in below.  But consistently soft stools can also be an indicator of bowel disease such as IBD.

Diarrhea or loose stool

A white or chalky color to the stool indicates a very high content of calcium, often found in dogs that are being fed raw with a high bone content.  If your dog is passing stools of this color, they are at risk of constipation from the bone material they are ingesting because of the dryness and risk of impaction.  In my practice, I am seeing  instances of poor mixing of raw foods and it usually from the same supplier – which is why I recommend only certain sources of food to my customers.

White chalky stools, an indicator of high bone content

If you see bright red blood in the stool, it’s also time to talk to your vet and of course, if you see visible worms than a vet visit is also recommended.

And finally, if your dog passes poos that are a neon green in color, they’ve been exposed to rat or mice poison and urgent attention is needed.

Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

 

Dog Poop Microbiome Predicts Canine Inflammatory Bowel Disease

Our gut microbiomes — the varieties of microbes living in our digestive tracts — may play a role in inflammatory bowel disease (IBD). Since dogs can also suffer from IBD, researchers at University of California San Diego School of Medicine analyzed fecal samples from dogs with and without the disease. They discovered a pattern of microbes indicative of IBD in dogs. With more than 90 percent accuracy, the team was able to use that information to predict which dogs had IBD and which did not. However, they also determined that the gut microbiomes of dogs and humans are not similar enough to use dogs as animal models for humans with this disease.

The study is published October 3, 2016 in Nature Microbiology.

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This French Bulldog, named Jorgie, has recently been diagnosed with IBD. A test based on this research would likely be more cost effective for diagnosis and lead to earlier detection. Photo: K Crisley, The Balanced Dog

“One of the really frustrating things about IBD in humans is that it’s hard to diagnose — it usually requires intestinal biopsies, which are not only imperfect, but invasive and expensive to collect,” said senior author Rob Knight, PhD, professor in the Departments of Pediatrics at UC San Diego School of Medicine and Computer Science and Engineering and director of the Center for Microbiome Innovation at UC San Diego.

According to Knight, most people with IBD have similar changes in the types of microbes living in their intestinal tracts, relative to healthy people. Yet it’s still difficult to discern healthy people from those with IBD just by looking at the microbes in their fecal samples. In addition, Knight said it’s not yet clear whether the microbial patterns associated with IBD contribute to the disease’s cause or are a result of the disease.

In a separate line of study, pets appear to be a conduit for microbe sharing in a house. Knight and collaborators previously found that microbial communities on adult skin are on average more similar to those of their own dogs than to other dogs. With a fair amount of precision, they can pick your dog out of a crowd based solely on overlap in your microbiomes.

In this latest study, Knight and team collected fecal samples from 85 healthy dogs and 65 dogs with chronic signs of gastrointestinal disease and inflammatory changes confirmed by pathology. To determine which microbial species were living in each sample, they used a technique Knight and collaborators popularized, called 16S rRNA sequencing, to quickly identify millions of bacterial species living in a mixed sample, based on the unique genes they harbor.

With this information, the researchers were able to look for similarities and differences in the microbial species found in IBD and non-IBD dogs. The differences were significant enough that they could distinguish IBD dog feces from non-IBD with more than 90 percent accuracy.

The researchers also compared the dog data to 2014 parallel findings in humans. The team found some similarities in the microbial interactions of IBD samples between dogs and humans, however the overlap was only partial. For example, Fusobacterium bacteria are associated with diseases in humans, but in dogs was associated with the non-IBD samples.

The study’s first author, Yoshiki Vázquez-Baeza, a graduate student in UC San Diego Jacobs School of Engineering’s Department of Computer Science and Engineering and a member of Knight’s lab, noted a potential limitation of the study — there were fewer healthy human samples than IBD samples in the 2014 human data set. But to best of their knowledge, he said, their statistical methods should not be affected by that.

“One of the really nice things about this study is that all of the statistical software packages we used to analyze data are available online, and anyone can see our exact calculations,” said Vázquez-Baeza. “Too often we read about a study with interesting conclusions, but it’s not completely clear how the authors got there. This approach is more open and transparent.”

This approach to diagnosing IBD in dogs is not yet available to veterinarians or dog owners, Vázquez-Baeza said. Moving forward, the researchers would like to study the overlap in IBD and non-IBD gut microbiomes among a series of animals. Zoo animals, for example, experience IBD more often than their wild counterparts, and studying them might help Knight, Vázquez-Baeza and team find key microbial players in IBD across species.

IBD is a family of diseases that includes ulcerative colitis and Crohn’s disease. IBD is characterized by chronic inflammation in the digestive tract, which can cause pain, severe diarrhea and weight loss. IBD can be debilitating and sometimes leads to life-threatening complications. The Centers for Disease Control and Prevention (CDC) estimate that more than 1 million Americans are living with IBD.

Source:  University of California San Diego media release